• Title/Summary/Keyword: Receptor methods

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The Association between Peroxisome Proliferator-Activated Receptor-Gamma C161T Polymorphism and Type 2 Diabetic Complications (제 2형 당뇨병 및 당뇨 합병증의 발생과 Peroxisome Proliferator-Activated Receptor-$\gamma2$ C161T 유전자 다형성과의 관계)

  • Lee, Byung-Cheol;Ahn, Se-Young;Doo, Ho-Kyung;Ahn, Young-Min
    • The Journal of Internal Korean Medicine
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    • v.28 no.4
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    • pp.902-910
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    • 2007
  • Objective : Peroxisome proliferator-activated receptor (PPAR)-gamma, a transcription factor in adipocyte differentiation, has important effects on insulin sensitivity, atherosclerosis, endothelial cell function and inflammation. Through these effects, PPAR-gamma2 might be involved with type 2 diabetes and vascular disease, including diabetic complications. Recently, it has been reported that the C161T polymorphism in the exon 6 of PPAR-gamma is associated with type 2 diabetes interacting with uncoupling protein 2 (UCP2) gene, and is associated with acute myocardial infarction. We studied the association of this polymorphism with type 2 diabetes and its complications, such as retinopathy, ischemic stroke, nephropathy and neuropathy in Korean non-diabetic and type 2 diabetic populations. Methods : Three hundred and thirty eight type 2 diabetic patients (retinopathy: 64, ischemic stroke: 67, nephropathy: 39 and neuropathy: 76) and 152 healthy matched control subjects were evaluated. The PPAR-gamma C161T polymorphism was analyzed by PCR-RFLP. Results : PPAR-gamma C161T genotype and allele frequency did not show significant differences between type 2 diabetic patients and healthy controls (T allele: 17.0 vs. 14.5, OR= 1.21, P=0.3188). In the analysis for diabetic complications, T allele in diabetic nephropathy was significantly higher than controls (P=0.0358). T allele in the ischemic stroke patients was also higher than healthy controls, although it had no significance (P=0.1375). Conclusions : These results suggest that the C161T polymorphism of the PPAR-gamma gene might be associated with diabetic nephropathy in type 2 diabetes.

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The Involvement of AMPA Receptor in the Antidepressant-like Effects of the Portulaca Oleracea L. Extract in Mice

  • Park, Soo-Jin;Choi, Min-Ji;Chung, Sun-Yong;Kim, Jong-Woo;Cho, Seung-Hun
    • Journal of Oriental Neuropsychiatry
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    • v.24 no.3
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    • pp.271-280
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    • 2013
  • Objectives : The development of natural drugs with antidepressant effects is important and needed. This study was performed to investigate the antidepressant-like effects of the distilled water extract of Portulaca oleracea L. (POL) in a mouse model and to investigate the role of ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in producing these antidepressant-like effects. Methods : The forced swim test (FST) and tail suspension test (TST) were used to investigate the behavioral anti-depressive-like effects of POL in mice. Additional behavioral experiments with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione, an AMPA receptor antagonist, were undertaken to determine the involvement of the antidepressant-like properties of POL in AMPA receptor throughput. Results : Oral administration of the POL extract (100 mg/kg) 1 h prior to testing significantly reduced the immobility times in the FST and TST. The antidepressant-like effects of the POL extract were not increased in a dose-dependent manner. Pre-treatment with NBQX significantly attenuated the reduction in immobility time induced by the POL extract in the FST. Conclusions : The distilled water extract of POL has antidepressant-like effects, which may be related to AMPA receptor. Pre-treatment with NBQX significantly attenuates the reduction in immobility time induced by the POL extract in the FST.

Effects of Agmatine on GABAA Receptor Antagonist-induced Tactile Allodynia (Agmatine이 GABAA 수용체 길항제로 유도한 촉각이질통에 미치는 효과)

  • Lee, Youn Woo;Ishikawa, Toshizo
    • The Korean Journal of Pain
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    • v.21 no.3
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    • pp.173-178
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    • 2008
  • Background: The intrathecal (IT) $GABA_A$ receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA. Methods: Male Sprague-Dawley rats, weighting 250-300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either $10{\mu}l$ of normal saline (NS) or agmatine ($30{\mu}g$ or $10{\mu}g$) in $10{\mu}l$ NS were injected 10 min prior to BIC ($10{\mu}g$) or NMDA ($5{\mu}g$). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean ${\pm}$ SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P < 0.05 was considered significant. Results: IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA. Conclusions: Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain.

Distribution of Glutamate Receptors in the Retina of the Greater Horseshoe Bat (Rhinolophus ferrumequinum) (한국관박쥐 망막에서 글루타메이트 수용체의 분포 양상)

  • Kwon, Oh-Ju;Jeon, Chang-Jin
    • Journal of Korean Ophthalmic Optics Society
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    • v.19 no.3
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    • pp.413-418
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    • 2014
  • Purpose: The objective of this study was analyzing the distribution of the excitatory neurotransmitter glutamate receptor to investigate the function in the retina of the greater horseshoe bat. Methods: After retinal tissues of adult greater horseshoe bat were cut into $40{\mu}m$ vertical sections, standard immuno-cytochemical techniques was applied for analysis. Immunofluorescence images were obtained using the Bio-Rad MRC 1024 laser scanning confocal microscope. Results: AMPA (GluR1-4), Kainate (GluR5-7, KA1-2) and NMDA (1, 2A, 2B) mainly distributed in the inner plexiform layer and outer plexiform layer. KA1 receptors have existed not only plexiform layer but also ganglion cell layer. Conclusions: The greater horseshoe bat has same neuron and neurotransmitter to mammalian retina. These findings suggest that bat has a functional retina for visual analysis.

Improving Effect of Extract of Ganoderma lucidum in Atherosclerosis from LDL Receptor Knockout Mouse (LDL Receptor Knockout Mouse에서 영지추출물의 죽상경화증 개선 효과)

  • Kwon, O Jun;Kim, MinYeong;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.31 no.1
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    • pp.17-23
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    • 2016
  • Objectives : This study was designed to protect effect on atherosclerosis through regulation of low density lipoprotein(LDL) by 70 % ethanol extract Ganoderma lucidum (GL) in LDL receptor knockout mouse (LDLr ko mice) fed Western diet.Methods : The LDLr ko mice were divided into 3 groups ; Control, GL100, and GL300. After grouping, LDLr ko mice were fed Western diet. The GL (100 or 300 mg/kg body weight/day, p.o.) was administered every day for 8 weeks. The body weight and food intake were measured every day. The changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) in serum were analyzed after experiment.Results : The LDLr ko mice fed Western diet were increased body weight gain and blood biochemistry parameters such as ALT, AST, TG, TC, and LDL. However GL300 group significantly reduced the body weight. Also TG, TC, and LDL level did not increase. The levels of ALT, AST, HDL were not changed. Also, LDLr ko mice model liver were observed lipid drop, but GL groups did not appear. Futhermore, histological analysis of GL groups aorta tissue were similar to NOR groups.Conclusions : We confirmed that whether GL administration is protect atherosclerosis or not. As the results, blood biochemistry and histological analysis did not changed much in GL administration groups. This study provides scientific evidence that GL protect the atherosclerosis through the reduction of LDL cholesterol. Therefore GL has potential medicine inhibition of atherosclerosis.

Expression and Clinical Significance of Sushi Domain-Containing Protein 3 (SUSD3) and Insulin-like Growth Factor-I Receptor (IGF-IR) in Breast Cancer

  • Zhao, Shuang;Chen, Shuang-Shuang;Gu, Yuan;Jiang, En-Ze;Yu, Zheng-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8633-8636
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    • 2016
  • Background: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domain containing protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation between the two proteins. Materials and Methods: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. Results: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normal breast tissue (P<0.05). The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r=0.553, P<0.01). Conclusions: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer.

ROLE OF NF${\kappa}B$ IN TOLL-LIKE RECEPTOR 9-MEDIATED MATRIX METALLOPROTEINASE-9 EXPRESSION (Toll-like receptor 9-매개에 의한 matrix metalloproteinase-9 발현에서 NF${\kappa}B$의 역할)

  • Lee, Sang-Hoon;Chin, Byung-Rho;Baek, Suk-Hwan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.6
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    • pp.636-642
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    • 2007
  • Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

Association of the 5-HT5A Receptor Gene Polymorphisms and Citalopram Response in Korean Patients with Major Depressive Disorder (한국인 주요우울증 환자에서의 세로토닌 5A 수용체의 유전자 다형성 및 Citalopram 치료반응과의 관련성)

  • Shim, Jin-Hyun;Paik, Jong-Woo;Oh, Jeung-Woong;Kang, Rhee-Hun;Lee, Hwa-Young;Lee, Min-Soo
    • Korean Journal of Biological Psychiatry
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    • v.15 no.4
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    • pp.303-309
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    • 2008
  • Objectives : Some reports have suggested that 5-HT5A polymorphism allelic association was associated with depression, however, there has been no report about relationship between the 5-HT5A gene and antidepressant response. We conducted the association study of the 5-HT5A receptor gene polymorphisms (-19G/C,12A/T) and response to citalopram in Korean patients with major depressive disorder(MDD). Methods : A total of 106 patients with major depressive disorder were included in this study. The patient's symptoms were measured by 21-item Hamilton Depression Rating Scale(HAMD) at baseline, week 1, week 2, week 4 and week 8 during citalopram treatment. A Responder to citalopram was defined by 50% reduction of total HAMD scores. To analyze genetic polymorphisms, a polymerase chain reaction based method was used. Results : At week 8, responders were 62, non-responders were 44. No significant differences of genotypes or allelic association in 19G/C and 12A/T polymorphisms were observed between responsive and non-responsive patients. Conclusion : These results do not support the hypothesis that this polymorphism of the HT5A receptor gene is involved in the therapeutic response to citalopram.

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Invasive Lobular Carcinoma: MRI Features and Clinicohistological Characteristics According to the ER, PR, and HER2 Statuses

  • Yoo, Eun Young;Nam, Sang Yu;Choi, Hye-Young;Cho, Hyun Yee
    • Investigative Magnetic Resonance Imaging
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    • v.19 no.3
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    • pp.137-145
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    • 2015
  • Purpose: To investigate correlations of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2) statuses with magnetic resonance imaging (MRI) features and clinicohistological characteristics in patients with invasive lobular carcinoma (ILC). Materials and Methods: Data from 64 histologically confirmed ILCs were analyzed retrospectively. Preoperative breast MRI was reviewed for morphology and dynamic contrast-enhanced kinetics of the tumor. Pathologic reports were reviewed for ER, PR, and HER2 positivity, tumor size, lymph node metastasis, and the number of metastatic lymph nodes. Furthermore, there was an investigation of the MRI features and clinicohistologic characteristics, according to the ER, PR, and HER2 statuses. Results: A significant difference in MRI features and clinicohistological tumor characteristics were observed only in relation to PR status. Of the 64 ILCs, 10 (15.6%) were PR negative. PR negative cancers, compared with PR positive cancers, were more likely to present as non-mass enhancement (P = 0.027); have a significantly larger mean tumor size ($5.00{\pm}1.05cm$ vs. $2.57{\pm}0.21cm$, P = 0.021); and have significantly more metastatic lymph nodes (P = 0.010). Conclusion: PR negative ILC presented more frequently as non-mass enhancement on MRI, with larger tumors and increased numbers of metastatic lymph nodes. Therefore, the PR status plays an important role in determining MRI features and clinicohistological characteristics of ILC.

Expression of p53 Breast Cancer in Kurdish Women in the West of Iran: a Reverse Correlation with Lymph Node Metastasis

  • Payandeh, Mehrdad;Sadeghi, Masoud;Sadeghi, Edris;Madani, Seyed-Hamid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1261-1264
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    • 2016
  • Background: In breast cancer (BC), it has been suggested that nuclear overexpression of p53 protein might be an indicator of poor prognosis. The aim of the current study was to evaluate the expression of p53 BC in Kurdish women from the West of Iran and its correlation with other clinicopathology figures. Materials and Methods: In the present retrospective study, 231 patients were investigated for estrogen receptor (ER) and progesterone receptor (PR) positivity, defined as ${\geq}10%$ positive tumor cells with nuclear staining. A binary logistic regression model was selected using Akaike Information Criteria (AIC) in stepwise selection for determination of important factors. Results: ER, PR, the human epidermal growth factor receptor 2 (HER2) and p53 were positive in 58.4%, 55.4%, 59.7% and 45% of cases, respectively. Ki67 index was divided into two groups: 54.5% had Ki67<20% and 45.5% had Ki67 ${\geq}20%$. Of 214 patients, 137(64%) had lymph node metastasis and of 186 patients, 122(65.6%) had vascular invasion. Binary logistic regression analysis showed that there was inverse significant correlation between lymph node metastasis (P=0.008, OR 0.120 and 95%CI 0.025-0.574), ER status (P=0.006, OR 0.080, 95%CI 0.014-0.477) and a direct correlation between HER2 (P=005, OR 3.047, 95%CI 1.407-6.599) with the expression of p53. Conclusions: As in a number of studies, expression of p53 had a inverse correlation with lymph node metastasis and ER status and also a direct correlation with HER2 status. Also, p53-positivity is more likely in triple negative BC compared to other subtypes.